Binding of hairpin pyrrole and imidazole polyamides to DNA: relationship between torsion angle and association rate constants.

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Abstract

N-methylpyrrole (Py)-N-methylimidazole (Im) polyamides are small organic molecules that bind to DNA with sequence specificity and can be used as synthetic DNA-binding ligands. In this study, five hairpin eight-ring Py-Im polyamides 1-5 with different number of Im rings were synthesized, and their binding behaviour was investigated with surface plasmon resonance assay. It was found that association rate (k(a)) of the Py-Im polyamides with their target DNA decreased with the number of Im in the Py-Im polyamides. The structures of four-ring Py-Im polyamides derived from density functional theory revealed that the dihedral angle of the Py amide carbonyl is 14∼18°, whereas that of the Im is significantly smaller. As the minor groove of DNA has a helical structure, planar Py-Im polyamides need to change their conformation to fit it upon binding to the minor groove. The data explain that an increase in planarity of Py-Im polyamide induced by the incorporation of Im reduces the association rate of Py-Im polyamides. This fundamental knowledge of the binding of Py-Im polyamides to DNA will facilitate the design of hairpin Py-Im polyamides as synthetic DNA-binding modules.

Journal

  • Nucleic acids research

    Nucleic acids research 40(22), 11510-11517, 2012-10-04

    Oxford University Press

Codes

  • NII Article ID (NAID)
    120005122357
  • NII NACSIS-CAT ID (NCID)
    AA00760269
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    0305-1048
  • Data Source
    IR 
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